Neuroendocrine regulation of inflammation

Abstract

The interaction between the sympathetic nervous system and the immune system has been documented over the last several decades. In this review, the neuroanatomical, cellular, and molecular evidence for neuroimmune regulation in the maintenance of immune homeostasis will be discussed, as well as the potential impact of neuroimmune dysregulation in health and disease.

Keywords: Adrenergic receptor; Beta2-adrenergic receptor; Neuroimmune; Norepinephrine; Stress; Sympathetic nervous system.

Figure 1

SNS signaling upon antigen exposure. Antigen introduction via injury or exposure allows for the release of inflammatory cytokines by phagocytic innate immune cells that stimulate the hypothalamus in the brain to activate preganglionic sympathetic neurons. Preganglionic sympathetic neurons synapse on postganglionic sympathetic neurons outside of the spinal cord and innervate lymphoid organs. NE is released from the sympathetic nerve terminals in the proximity of immune cells that express the β₂AR. In addition to the autonomous ability of immune cells themselves to regulate their own activity, the effects induced after β₂AR stimulation on immune cells provide a mechanism by which immune homeostasis is maintained.

Figure 2. Known mechanisms of IgG₁ and IgE regulation in B cells

(1) The IgG₁ increase that is mediated by β₂AR stimulation follows the classical G_α stimulatory pathway that results in phosphorylation of CREB and mediates transcription of downstream targets, including OCA-B, Oct-2, and IgG₁ (2) The β₂AR-associated IgE increase is mediated through the PKA/HePTP/p38 MAPK pathway. The existence of these divergent pathways suggests a differential mechanism by which the enhancement of IgG₁ and IgE is regulated.